Abstract
Short-chain fatty acids (SCFAs), produced by anaerobic fermentation of mainly indigestible dietary carbohydrates by gut microbiota, have a profound influence on intestinal function and host energy metabolism. Antibiotics may seriously disturb the balance of fecal SCFAs. To evaluate the impacts of antibiotics on fecal SCFAs produced by gut microbiota, a simple, reproducible and accurate gas chromatography (GC) method, which can simultaneously analyze seven SCFAs in fecal samples, was developed and validated. The ranges of detection and quantitation of the SCFAs reached 0.0868 ~ 0.393 and 0.261 ~ 1.18 μg·mL-1 respectively, in an optimized protocol for SCFAs extraction and analysis that used 10 mL 75% ethanol aqueous solution containing 1% HCl, without ultrasonication. The technique exhibited excellent intra-day (relative standard deviation (RSD) ≤ 2.54%) and inter-day (RSD ≤ 4.33%) precisions for all the SCFAs. Later, we administered broad-spectrum antibiotics, cefdinir or azithromycin to rats and analyzed the alterations in fecal SCFAs. The total amount, types and distribution of nearly all fecal SCFAs were significantly altered during the administration and even after withdrawal of the antibiotics in rats. The effects of cefdinir on the SCFAs were more pronounced than those of azithromycin. Our findings suggest SCFAs may serve as sensitive indicators to monitor the influences of antibiotics on SCFAs originated by intestinal bacteria. Our improved SCFAs analysis method is a potential platform for a standard clinical test of the effects of new antibiotics on SCFAs.
Highlights
Gut microbiota, a complex microbial community densely inhabits in the intestinal tract, plays essential roles in our health via multiple mechanisms, one of which is to provide functional metabolites for the host
We found all the SCFAs decreased upon cefdinir or azithromycin treatment and most of the SCFAs did not recover to control levels within 8 days after withdrawal of the antibiotics
Propionate is a primary precursor for gluconeogenesis and it reduces the synthesis of hepatic cholesterol [40]
Summary
A complex microbial community densely inhabits in the intestinal tract, plays essential roles in our health via multiple mechanisms, one of which is to provide functional metabolites for the host. Short-chain fatty acids (SCFAs) are major end-products of anaerobic fermentation by microbiota in the large intestine, including acetic acid, propionic acid, PLOS ONE | DOI:10.1371/journal.pone.0167032. Propionic acid is mainly produced by Bacteroides and Propionibacterium through succinate pathway [5]. A recent study showed that most dominant species of the Bacteroides positively associated with fecal concentrations of isovaleric and isobutyric acid, which are negatively correlated with blood levels of triglycerides [8]. Recent studies indicate that SCFAs are produced by gut microbial fermentation of dietary fiber [20], compared to the plant-based diet, an animal-based diet resulted in significantly lower levels of the products of carbohydrate fermentation [18]
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